JACS Au最新文献 - Book学术

Signaling Mechanism of Cuproptosis Activating cGAS-STING Immune Pathway 杯突激活 cGAS-STING 免疫途径的信号机制

JACS Au Pub Date : 2024-09-20 DOI: 10.1021/jacsau.4c00712

Chengyuan Zhu, Jialiang Li, Wanying Sun, Desheng Li, Yiliang Wang, Xing-Can Shen

{"title":"Signaling Mechanism of Cuproptosis Activating cGAS-STING Immune Pathway","authors":"Chengyuan Zhu, Jialiang Li, Wanying Sun, Desheng Li, Yiliang Wang, Xing-Can Shen","doi":"10.1021/jacsau.4c00712","DOIUrl":"https://doi.org/10.1021/jacsau.4c00712","url":null,"abstract":"Copper-mediated programmed cell death, which influences the regulation of tumor progression, is an effective approach for antitumor molecular therapy. Unlike apoptosis, copper complex-induced cuproptosis by lipid-acylated protein aggregation triggers the mitochondrial proteotoxic stress response, which could be associated with immunomodulation. However, it remains a great challenge to understand the distinctive molecular mechanisms that presumably activate immunity by cuproptosis. Here, the new nonlabeling fluorescent molecular tools of Cu-DPPZ-Py+ and Cu-DPPZ-Ph are synthesized and used to investigate the differential immune signaling mechanisms induced by copper-mediated cuproptosis or apoptosis. With Cu-DPPZ-Py+ and Cu-Elesclomol, there is strong evidence that the triggering cuproptosis significantly drives mitochondrial DNA (mtDNA) release to activate innate immunity via cyclic GMP-AMP synthase-stimulation of interferon genes (cGAS-STING), which can improve T cell antitumor immunity in vivo. By contrast, it is observed that Cu-DPPZ-Ph treated tumor cells could release intracellular caspase-3, resulting in apoptosis-associated immunosuppression. This study supports insights into how cuproptosis bridges cGAS-STING immune pathways, contributing to the development of cuproptosis-based antitumor immunotherapy.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoupling Electrolytic Water Splitting by an Oxygen-Mediating Process 通过氧媒介过程解耦电解水分离

JACS Au Pub Date : 2024-09-19 DOI: 10.1021/jacsau.4c00710

Mingze Xu, Jianying Wang, Shi-Gang Sun, Zuofeng Chen

{"title":"Decoupling Electrolytic Water Splitting by an Oxygen-Mediating Process","authors":"Mingze Xu, Jianying Wang, Shi-Gang Sun, Zuofeng Chen","doi":"10.1021/jacsau.4c00710","DOIUrl":"https://doi.org/10.1021/jacsau.4c00710","url":null,"abstract":"Decoupled water electrolysis systems, incorporating a reversible redox mediator that allows for the construction of membrane-free electrolyzers, have emerged as a promising approach to produce high-purity hydrogen with remarkable flexibility. The key factor crucial for practical applications lies in the development of mediator electrodes that possess suitable redox potential, high redox capacity, excellent cycling reversibility and stability. Herein, we introduce a novel concept of oxygen-mediating redox mediators (ORMs) employing Bi2O3 as an example material, which are capable of sequestering oxygen during the hydrogen evolution reaction and subsequently releasing it to generate oxygen gas under alkaline conditions. Thanks to its remarkable reversible redox activity and specific capacity, the Bi2O3 electrode boasts an impressive reversible specific capacity of 300.8 mA h g–1 and delivers outstanding cycling performance for >1000 cycles at a current density of 2.0 A g–1. Furthermore, the implementation of such a decoupled alkaline water electrolysis system can be integrated with a Bi2O3–Zn battery, enabling both power-to-fuel (hydrogen production) and chemical-to-power (rechargeable Bi2O3–Zn battery) conversion. With many oxygen-carrier materials readily available and the potential integration with rechargeable alkaline batteries, this study provides an alternative competitive route for membrane-free decoupled water splitting through the oxygen-mediating mechanism with combined energy transformation and storage.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N2 Dissociation vs Reversible 1,2-Methyl Migration in PCNHCP Cobalt(I) Complexes in the Stereoselective Isomerization (E/Z) of Allyl Ethers PCNHCP 钴（I）配合物在烯丙基醚立体选择性异构化（E/Z）过程中的 N2 离解与 1,2-甲基可逆迁移的关系

JACS Au Pub Date : 2024-09-18 DOI: 10.1021/jacsau.4c00529

Sakthi Raje, Subhash Garhwal, Katarzyna Młodzikowska-Pieńko, Tofayel Sheikh Mohammad, Ron Raphaeli, Natalia Fridman, Linda J. W. Shimon, Renana Gershoni-Poranne, Graham de Ruiter

引用次数: 0

Selectivity of Complex Coacervation in Multiprotein Mixtures 多蛋白混合物中复合共沉淀的选择性

JACS Au Pub Date : 2024-09-17 DOI: 10.1021/jacsau.4c00399

So Yeon Ahn, Allie C. Obermeyer

{"title":"Selectivity of Complex Coacervation in Multiprotein Mixtures","authors":"So Yeon Ahn, Allie C. Obermeyer","doi":"10.1021/jacsau.4c00399","DOIUrl":"https://doi.org/10.1021/jacsau.4c00399","url":null,"abstract":"Liquid–liquid phase separation of biomolecules is increasingly recognized as being relevant to various cellular functions, and complex coacervation of biomacromolecules, particularly proteins, is emerging as a key mechanism for this phenomenon. Complex coacervation is also being explored as a potential protein purification method due to its potential scalability, aqueous operation, and ability to produce a highly concentrated product. However, to date, most studies of complex coacervation have evaluated the phase behavior of a binary mixture of two oppositely charged macromolecules. Therefore, a comprehensive understanding of the phase behavior of complex biological mixtures is yet to be established. To address this, a panel of engineered proteins was designed to allow for quantitative analysis of the complex coacervation of individual proteins within a multicomponent mixture. The behavior of individual proteins was evaluated using a defined mixture of proteins that mimics the charge profile of the Escherichia coli proteome. To allow for the direct quantification of proteins in each phase, spectrally separated fluorescent proteins were used to construct the protein mixture. From this quantitative analysis, we observed that protein coacervation was synchronized in the mixture, which was distinctive from the behavior when each protein was evaluated in a single-protein system. Subtle differences in biophysical properties between the proteins, such as the ionization of individual charged residues and overall charge density, became noticeable in the mixture, which allowed us to elucidate parameters for protein complex coacervation. With this understanding, we successfully designed methods to enrich a range of proteins of interest from a mixture of proteins.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unleashing the Potential: High Responsivity at Room Temperature of Halide Perovskite-Based Short-Wave Infrared Detectors with Ultrabroad Bandwidth 释放潜能：基于卤化物包晶的超宽带宽短波红外探测器在室温下的高响应率

JACS Au Pub Date : 2024-09-17 DOI: 10.1021/jacsau.4c00621

Yuqin Qian, Zhi-Chao Huang-Fu, Hao Li, Tong Zhang, Xia Li, Sydney Schmidt, Haley Fisher, Jesse B. Brown, Avetik Harutyunyan, Hanning Chen, Gugang Chen, Yi Rao

{"title":"Unleashing the Potential: High Responsivity at Room Temperature of Halide Perovskite-Based Short-Wave Infrared Detectors with Ultrabroad Bandwidth","authors":"Yuqin Qian, Zhi-Chao Huang-Fu, Hao Li, Tong Zhang, Xia Li, Sydney Schmidt, Haley Fisher, Jesse B. Brown, Avetik Harutyunyan, Hanning Chen, Gugang Chen, Yi Rao","doi":"10.1021/jacsau.4c00621","DOIUrl":"https://doi.org/10.1021/jacsau.4c00621","url":null,"abstract":"Short-wave infrared (SWIR) imaging systems offer remarkable advantages, such as enhanced resolution and contrast, compared to their optical counterparts. However, broader applications demand improvements in performance, notably the elimination of cryogenic temperature requirements and cost reduction in manufacturing processes. In this manuscript, we present a new development in SWIR photodetection, exploiting the potential of metal halide perovskite materials. Our work introduces a cost-effective and easily fabricated SWIR photodetector with an ultrabroad detection range from 900 to 2500 nm, a room-temperature responsivity of 1.57 × 102 A/W, and a specific detectivity of 4.18 × 1010 Jones at 1310 nm. We then performed comprehensive static and time-resolved optical and electrical measurements under ambient conditions, complemented by extensive density functional theory simulations, validating the formation of heterojunctions within the intrinsic n-type and extrinsic p-type perovskite structures. The potential of our perovskite-based SWIR materials extends from photodetectors to photovoltaic cells and introduces a possibility for high SWIR responsivity at room temperature and atmospheric pressure, which promotes its economic efficiency.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

19F NMR-Based Chiral Analysis of Organoboron Compounds via Chiral Recognition of Fluorine-Labeled Boronates with Cobalt Complexes 通过钴配合物对氟标记硼酸盐的手性识别进行基于 19F NMR 的有机硼化合物手性分析

JACS Au Pub Date : 2024-09-16 DOI: 10.1021/jacsau.4c00703

Hahyoun Park, Cham Bi Seo, Jaesook Yun, Hyunwoo Kim

引用次数: 0

From Data to Discovery: Recent Trends of Machine Learning in Metal–Organic Frameworks 从数据到发现：金属有机框架中机器学习的最新趋势

JACS Au Pub Date : 2024-09-12 DOI: 10.1021/jacsau.4c00618

Junkil Park, Honghui Kim, Yeonghun Kang, Yunsung Lim, Jihan Kim

引用次数: 0

Metal-free Borylation of α-Naphthamides and Phenylacetic Acid Drug α-萘酰胺和苯乙酸类药物的无金属硼酸盐化作用

JACS Au Pub Date : 2024-09-11 DOI: 10.1021/jacsau.4c00660

Suman Maji, Parveen Rawal, Animesh Ghosh, Karishma Pidiyar, Shaeel A. Al-Thabaiti, Puneet Gupta, Debabrata Maiti

引用次数: 0

Rational Design of Dual-Domain Binding Inhibitors for N-Acetylgalactosamine Transferase 2 with Improved Selectivity over the T1 and T3 Isoforms 合理设计双域结合型 N-乙酰半乳糖胺转移酶 2 抑制剂，提高对 T1 和 T3 异构体的选择性

JACS Au Pub Date : 2024-09-11 DOI: 10.1021/jacsau.4c00633

Ismael Compañón, Collin J. Ballard, Erandi Lira-Navarrete, Tanausú Santos, Serena Monaco, Juan C. Muñoz-García, Ignacio Delso, Jesus Angulo, Thomas A. Gerken, Katrine T. Schjoldager, Henrik Clausen, Tomás Tejero, Pedro Merino, Francisco Corzana, Ramon Hurtado-Guerrero, Mattia Ghirardello

{"title":"Rational Design of Dual-Domain Binding Inhibitors for N-Acetylgalactosamine Transferase 2 with Improved Selectivity over the T1 and T3 Isoforms","authors":"Ismael Compañón, Collin J. Ballard, Erandi Lira-Navarrete, Tanausú Santos, Serena Monaco, Juan C. Muñoz-García, Ignacio Delso, Jesus Angulo, Thomas A. Gerken, Katrine T. Schjoldager, Henrik Clausen, Tomás Tejero, Pedro Merino, Francisco Corzana, Ramon Hurtado-Guerrero, Mattia Ghirardello","doi":"10.1021/jacsau.4c00633","DOIUrl":"https://doi.org/10.1021/jacsau.4c00633","url":null,"abstract":"The GalNAc-transferase (GalNAc-T) family, consisting of 20 isoenzymes, regulates the O-glycosylation process of mucin glycopeptides by transferring GalNAc units to serine/threonine residues. Dysregulation of specific GalNAc-Ts is associated with various diseases, making these enzymes attractive targets for drug development. The development of inhibitors is key to understanding the implications of GalNAc-Ts in human diseases. However, developing selective inhibitors for individual GalNAc-Ts represents a major challenge due to shared structural similarities among the isoenzymes and some degree of redundancy among the natural substrates. Herein, we report the development of a GalNAc-T2 inhibitor with higher potency compared to those of the T1 and T3 isoforms. The most promising candidate features bivalent GalNAc and thiophene moieties on a peptide chain, enabling binding to both the lectin and catalytic domains of the enzyme. The binding mode was confirmed by competitive saturation transfer difference NMR experiments and validated through molecular dynamics simulations. The inhibitor demonstrated an IC50 of 21.4 μM for GalNAc-T2, with 8- and 32-fold higher selectivity over the T3 and T1 isoforms, respectively, representing a significant step forward in the synthesis of specific GalNAc-T inhibitors tailored to the unique structural features of the targeted isoform.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Different DNA Binding and Damage Mode between Anticancer Antibiotics Trioxacarcin A and LL-D49194α1 抗癌抗生素 Trioxacarcin A 和 LL-D49194α1 的不同 DNA 结合和损伤模式

JACS Au Pub Date : 2024-09-10 DOI: 10.1021/jacsau.4c00611

Ruo-Qin Gao, Xiao-Dong Hu, Qiang Zhou, Xian-Feng Hou, Chunyang Cao, Gong-Li Tang

{"title":"Different DNA Binding and Damage Mode between Anticancer Antibiotics Trioxacarcin A and LL-D49194α1","authors":"Ruo-Qin Gao, Xiao-Dong Hu, Qiang Zhou, Xian-Feng Hou, Chunyang Cao, Gong-Li Tang","doi":"10.1021/jacsau.4c00611","DOIUrl":"https://doi.org/10.1021/jacsau.4c00611","url":null,"abstract":"Trioxacarcin A (TXN) is a highly potent cytotoxic antibiotic with remarkable structural complexity. The crystal structure of TXN bound to double-stranded DNA (dsDNA) suggested that the TXN interaction might depend on positions of two sugar subunits on the minor and major grooves of dsDNA. LL-D49194α1 (LLD) is a TXN analogue bearing the same polycyclic polyketide scaffold with a distinct glycosylation pattern. Although LLD was in a phase I clinical trial, how LLD binds to dsDNA remains unclear. Here, we solved the solution structures at high resolutions of palindromic 2″-fluorine-labeled guanine-containing duplex d(A1A2C3C4GFGFT7T8)2 and of its stable LLD and TXN covalently bound complexes. Combined with biochemical assays, we found that TXN-alkylated dsDNA would tend to keep DNA helix conformation, while LLD-alkylated dsDNA lost its stability more than TXN-alkylated dsDNA, leading to dsDNA denaturation. Thus, despite lower cytotoxicity in vitro, the differences of sugar substitutions in LLD caused greater DNA damage than TXN, thereby bringing about a completely new biological effect.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0